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DNA-based nanosensors for cancer diagnosis and treatment

Sensors composed of DNA molecules could be used for personal cancer treatments and for monitoring the quality of stem cells - this is according to the words of an international team of researchers led by scientists from an American and Italian university

Sensors composed of DNA molecules could be used for personalized cancer treatments and for monitoring the quality of stem cells. Image: University of California at Santa Barbara
Sensors composed of DNA molecules could be used for personalized cancer treatments and for monitoring the quality of stem cells. Image: University of California at Santa Barbara

Sensors composed of DNA molecules could be used for personal cancer treatments and for monitoring the quality of stem cells - this is according to the words of an international team of researchers led by scientists from an American and Italian university.

The innovative nanosensors are able to quickly locate a broad family of proteins called transcription factors, which function as the main control switches of life. The findings of the new study were published in the scientific journal Journal of the American Chemical Society.

"The fate of our cells is controlled by thousands of different proteins, called transcription proteins," said Alexis Vallée-Bélisle, a researcher from the Department of Chemistry and Biochemistry at the University of California, Santa Barbara, who led the study. "The role of these proteins is to read the genome and translate it into instructions for the synthesis of the various molecules that make up and control the cell's activity. Transcription factors function as switches of our cells, similar to the switches found in our cell phones and computers. What our sensors do is read these switches."

When scientists turn stem cells into cells with a defined specialization, they do so by changing the concentration of several transcription factors, explains one of the researchers. This process is known as reprogramming the cells. "Our sensors monitor the activity of the transcription factors, and can be used to ensure that the stem cells have indeed been properly reprogrammed," the researcher notes. "They could also be used to identify the transcription factors that were activated or suppressed in the cancer cells of any patient, thus allowing doctors to use the appropriate combination of drugs for each and every patient."

The researchers note that many laboratories have tested ways to read transcription factors; However, the approach of this research team is extremely fast and convenient. "In most laboratories, researchers spend hours extracting these proteins from the cells before testing them," notes the researcher. "Using our new sensors, we simply crush the cells, insert our sensors into this mixture, and measure the fluorescence level of the sample."

The research began when one of the researchers realized that all the information needed to detect the activity of the transcription factors is already encoded in the human genome, and it could be used to develop sensors. "During the activation of the sensor, thousands of these different factors bind to the DNA sequences that correspond to them in a selective manner," explains the researcher. "We used these sequences as a starting point for building our innovative nanosensors."

The breakthrough behind this technology came from studies about natural biosensors found in the cells themselves. "All living things, from bacteria to humans, monitor their environmental conditions using "biomolecular switches" - shape-changing molecules composed of RNA or proteins," explains the researcher. "For example, in our sinuses, there are millions of receptor proteins that locate different odor molecules by switching from the "off" state to the "on" state. The beauty of these switches is that they are small enough to operate inside a cell, and selective enough to operate in the very complex environments that exist there." While receiving inspiration from the efficiency of these natural nanosensors, the research group began to build synthetic signaling nanosensors using DNA molecules, instead of protein or RNA molecules.

More specifically, the team re-engineered three natural DNA sequences, each of which recognizes a different transcription factor, into molecular switches that become fluorescent when bound to their intended targets. Using these nanometer sensors, the researchers were able to determine the activity of each of these transcription factors directly from the cell extracts simply by measuring their fluorescence level.

The researchers believe that their approach will eventually allow biologists to monitor the activity of thousands of transcription factors, which will lead to a better understanding of the mechanisms underlying cell division and their development. "Alternatively, since these nanosensors work directly in biological samples, we also believe that they could be used to sort and test new drugs that could, for example, inhibit the binding activity activated by a transcription factor responsible for the growth of cancer cells," adds the researcher.
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